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EXCELLENCE EXPERTISE INNOVATION
TB Free Marshall IslandsEbeye and Majuro, Republic of Marshall Islands,
2017-2018
Janice Louie, MD, MPHMedical Consultant Meeting
San Antonio, TXNovember 29-30, 2018
Janice Louie, MD, MPH has the following disclosures to make:
• No conflicts of interest
• No relevant financial relationships
Disclosures
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TB-Free Marshall IslandsEbeye and Majuro, Republic of the Marshall Islands, 2017-18
Janice Louie, MD, MPHMedical Director
San Francisco Department of Public Health Tuberculosis Clinic
Where are the Marshall Islands?
• Comprised of 1156 islands, 29 coral atolls surrounding a 655 sqmi lagoon
• Population 53,376 (2016)• Main inhabited islands are
Majuro or Ebeye atolls
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Why do we care about the Marshall Islands?
• “Discovered” by Spanish in 1500s, occupied by Japan in WW2, became a US territory 1944-1979
• In 1986 under the “Compact of Free Association” Republic of Marshall Islands (RMI) became a sovereign stateoUS provides direct assistance (renewed in 2003, 3.5 billion until 2023)
oUS provides infrastructure: health, education, and defense until 2023
oMarshallese have unique legal status: maintain their citizenship, but may travel and work in the US • ~18-20,000 Marshallese live in the US- the majority (~12,000) have settled in Springdale,
Arkansas
• Net emigration of ~952 Marshallese to US annually (1.7%), mostly for jobs
Majuro
• Capital of RMI• Population ~27,797• Land mass 10 square
miles• Per capita income $2700• Main exports are frozen
fish (tuna), coconuts, ornamental clams and shells, and handicrafts
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Kwajalein Atoll and Ebeye Island
Ebeye• Population ~10,000• 0.14 square miles• “Slum of the Pacific”
Kwajalein Atoll• Population ~1000
military and families• 1.2 square miles• Leased by US army
until 2066• Main income
generator for all of RMI ($15 million annually)
Ronald Reagan Ballistic Missile Defense Test Site
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Bikini Atoll 1954, “Castle Bravo”
Between 1946-1958 the US dropped (tested) 67 nuclear bombs on Bikini and Enewetak atolls. The explosive yield was equivalent to 1.6 Hiroshima bombs detonated every day over the course of 12 years
The US Legacy of Nuclear Testing
• Communities downwind were exposed to deadly radioactive ash; nearby island residents describe how “it snowed for the first time in the islands”
• Nuclear fallout prompted a mass exodus to other islands and the US
• A 2004 U.S. National Cancer Institute study found the entire island nation remains affected. Radiation levels remain double the safe standard.
• The Compact allowed for settlement of claims against the US, as the fund is depleted current allocation is $98 quarterly per evacuated resident
Bikini Town Hall
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• 1969-79: As part of the clean-up of 3 of 40 islands, 111,000 cubic yards of radioactive waste was placed under a concrete dome, including plutonium (half-life 24,000 years).
• Due to rising sea levels, cracks are now appearing in the dome and trace plutonium has been detected in Chinese rivers.
Global warming and a rising sea
• Island currently 6 feet above sea level
• Over the past 30 years sea level has risen 1 foot
• Periodic extreme high tides destroy and flood homes
• Ten rows of this cemetery are now underwater
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Demographics• Median age: 20.6 years
o 40% under age 14o 53% under age 24
• Average 6.8 persons/household
• Female mean age at birth of first child: 20.7 years• Adolescent birth rate (age 15-19 years): 85/1000
• Average 4.1 children born/female• Infant mortality rate 22/1000 (#83; US ~5.8/1000)
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Life expectancy: 73.4 years
• Overweight or obese: 62% (4th in world)
• Diabetes prevalence: 40% (compare to 9.3% in US)
• Hypertension: 60%
• HIV prevalence: <0.1 %
The Compact supplemental food program supplies processed foods such as Spam, flour and canned goods…
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• Unemployment rate 36%
o High rates of alcoholism (20%, 65% endorse binge drinking) and suicide in males (teens and young adults)
Marshallese DietFish, chicken, coconut, breadfruit, pandana, white rice, spam
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Fresh fruits and vegetables are imported
• Electricity spotty, frequent blackouts
• No reliable supply of potable water leads to high rate of gastrointestinal illnesses
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Most households rely on collected rainwater or must purchase filtered water to carry home
RMI is highly dependent on foreign aid ($40 million annual revenue, 64% comes from grants from US, Taiwan, and Japan)
Periodic donations not contributing to infrastructure or sustainable change.
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Poor standard of living, crowding, lack of sanitation, clean water, and healthy diet, and high rates of obesity and diabetes leads to……
TB program rates reported to CDC under the CDC cooperative agreement
RMI ranks 3rd in tuberculosis deaths per capita
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WHO Publication WF220 (2013)
WHO recommendation Method 7, Option 3b
1. “Systematic screening for active TB may be considered for geographically defined subpopulations with extremely high levels of undetected TB (>1% prevalence*)
2. “Systematic screening for active TB may be considered for subpopulations that have very poor access to healthcare, such as people living in slums, homeless people, people living in remote areas with poor access to healthcare, and other vulnerable groups including some indigenous populations, migrants and refugees”
*The risk of false positive diagnosis increases as prevalence declines, therefore special attention should be paid to diagnostic accuracy particularly when prevalence is <1%
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= more accurate and specific diagnosis, resulting in more efficient use of resources and labor
4X method: sX+ cXr + geneXpert+ eXpertise
Comstock et al, A Controlled Trial of Community-Wide Isoniazid Prophylaxis in Alaska. Am Rev Resp Dis un;95(6):935-43
Community intervention of INH prophylaxis in Native Alaskans• N= ~7300• Remote areas• Poor access to
healthcare• All treated with INH for
12 months regardless of TST status
• Marked decrease in number of active cases over ensuring 5 years
• Almost no cases observed in children <5 years
Not only screen, but move toward elimination?
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Ideal Objectives of Mass Screening for Active TB
• Detect active TB cases early• Reduce poor treatment outcomes, long term health problems, and adverse social
and economic consequences of TB for the individual• Reduce TB transmission by shortening the duration of infectiousness
• Prevent active TB in household contacts
• Active case finding in high risk persons (diabetes)
• Work shoulder-to-shoulder with experts
• Introduce new technology (geneXpert)
• Launchpad for an enhanced TB control program
• Capacity building
Caveats with Mass Screening for Active TB
• Expensive for a few TB cases found; important to limit to high risk populations
• Chest X-ray screening can over-diagnose and over-treat non-TB
• Depends on local resources (equipment, personnel)
• Can overwhelm existing program with new cases
• Short-benefits only if not accompanied by program expansion (especially for latent TB) and repeat screening events
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Feb-April 2017:TB-Free EbeyeProject
• Population ~10,000
• 3 month screening
• Age ≥18 years• Identification
and treatment of active TB cases
• LTBI treatment of contacts
TB-Free Ebeye 2017Adults only
25.9%
Active
National Tuberculosis Controllers Association Conference, Palm Springs, CA. May 2018
22.3%
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Model: Sustainable Change in Ebeye
• March 2018: • TB incidence on track to be less than
half of prior 3 years• Despite tripling the number of TB
cases managed by the program, TB death rate was reduced by ~80% (compared to 2010-2013)
• Current focus is on prevention• >200 persons placed on LTBI
treatment in past year• Staffing increases put in place by
mass screening have remained in place under the local budget (6 staff in Jan 2017 to 20 staff currently)
Slide courtesy of R Brostom
TB-Free Majuro• May-November 2018• Focus on active AND LTBI in all ages• Rotating screening sites throughout the island
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• Two teams screening 250-300 people/day• 3 mobile X-ray machines (2 donated by Japan)• Hire 7 new local permanent staff (2 nurses, 5
DOT) and many temporary staff• 8 volunteer rotations• 93 volunteers from US, Canada, Australia,
Phillipines, Taiwan, Fiji, Palau, Federated States of Micronesia
• Expect to diagnose and treat 200+ active TB cases and 5000+ LTBI cases
• Anticipate 300-400,000 tablets of rifapentineneeded (purchased at discount rate from Sanofi)
Management of Logistics Critical
Majuro elementary school screening site
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1. Registration (fingerprint)
Mask if you have a cough
2. TST placement
* 250-300 placed daily**BCG vaccination is routine in the Republic of Marshall Islands
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3. TST read 48 hours later 4. If TST positive, also check for diabetes,HTN and hyperlipidemia, ask about ETOH and tobacco use
5. Pediatric exam
Regardless of TST result, if age <10 years, child sent to pediatric exam station for lymph node and Hansen’s disease check
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6. X-ray and skin exam for Hansen’s Disease (Leprosy)• anyone over 10 years or <10 years with symptoms or exposure
7. CXR interpretation by MD to determine if latent vs possible active TB • Average 150-200 CXR daily per reader
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8. If CXR normal and TST positive, counsel and treat for LTBI
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9. If CXR is abnormal, sputum collected
Algorithm for Suspect Active Cases: • First sputa collected on-site sent for geneXp testing at Majuro Hospital (sometime induced)• CHOW collects second and third sputa at patient’s home (ideally in AM) to be sent to Hawaii for smear and culture.
10. Case conference: all abnormal CXRs and geneXp results reviewed, treatment decisions made
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Marshall Islands normal
The assignment:Identify chest X-rays with lesions• suggestive of
active TB disease OR
• compatible with TB (active or inactive)
Suggestive of active TB
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Suggestive of active TB
Suggestive of active TB
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Suggestive of active TB
Compatible with TB (active or inactive)?
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Compatible with TB (active or inactive)?
Compatible with TB (active or inactive)?
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Compatible with TB (active or inactive)?
Compatible with TB (active or inactive)?
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Compatible with TB (active or inactive)?
Typical Case Presentation• Asymptomatic• Never treated for TB
but thinks a nephew who lived in the same house 3 years ago may have taken TB pills
• Seems to be lot of people coughing in the neighborhood
• No prior chest X rays or record of TB treatment
• Long term smoker• GeneXpert negative
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LTBI Treatment Checklist
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11. Directly Observed Therapy
Managing and packing medications: a laborious but critical task: 3HP (once weekly) or INH/RIF (daily)
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October 26, 2018Preliminary Results:
• 81% screened (n=22,104)
• 285 active cases
• 5286 LTBI cases (24%); 4564 started on treatment (3HP)
• 54 new leprosy cases (incidence 24/10,000)
Preliminary Results: Active Case Finding
• Screening is currently ongoing
• As of September 2, 56% of the population had completed TB screening
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Caveats
• Data still coming in, but based on Ebeye results….
• Opportunity for a young TB control program to identify possible gaps in laboratory testing by performing QA on specimen collection, transport, and local geneXp methods• May be difficult to improve culture yield based on flights from RMI to
Honolulu only go three times weekly
Possible causes of low culture yield:
In India, positive cultures after storage at room temp:• 3 days: 83%• 5 days: 71%• 7 days: 63%
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2017
2018
USAPI Transport times to Honolulu
Pacific Island TB Controllers Association (PITCA) Meeting– Honolulu, Hawaii – September 2017
• Transport time of RMI specimens longer than recommended (especially Ebeye, which may explain low yield)
• Temperature control during specimen storage is important
2018 submissions to Hawaii commercial laboratory: contamination rates
Pacific Island TB Controllers Association (PITCA) Meeting– Honolulu, Hawaii – September 2017
Possible proxy: Contamination rates increase with time of transport: • 3 days-7%• 5 days- 12%• 7 days- 18%
Paramasivan et al, Tubercle 1983
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TB-Free Majuro Summary: Lessons and Challenges
• Drew international attention to TB in the Marshall Islands and Marshallese in the US
• Built TB infrastructure for screening, diagnosis, laboratory testing and contact investigation
• Hands-on training by experts in the field
• Identified opportunities for program improvement
• Results of mass screening: >80% of population screened (goal 85%)
o > 285 diagnosed with active TB and started on treatment (~1.3%)
o Extraordinarily high incidences in young children
o ~5200 (28%) diagnosed with LTBI (TST+), >85% started on 3-HP
o54 newly diagnosed with leprosy ( rate 24.4/10,000)
TB-Free Majuro Summary: Lessons and Challenges
• Overdiagnosis? most active cases initially diagnosed clinically/radiographically o May need to adjust case numbers once all data available, but still identified a high TB
prevalence
• Overdiagnosis? all LTBI cases diagnosed by +TST in setting of BCG vaccinationo Although numbers are similar to those seen in Marshallese in Arkansas
• Jury still out: o Incidence of adverse events in a population with ?hep B prevalence and likely high
prevalence of ETOHo Possible under-dosing in an obese population - ?Efficacy down the line of treatment and
prophylaxiso Will the same decrease in TB incidence and TB-related mortality observed in Ebeye be
seen in Majuro?o Long-term impact and sustainability
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Group C Volunteers, TB-Free Majuro 2018
Thank you: Barbara Seaworth, Richard Brostrom, Pennan Barry, Ed Desmond, John Bernardo and Jon Warkentin
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Diagnostic Test Sensitivity (%, CI) Specificity (%, CI)
Liquid culture (GOLD standard) 100 100
Sputum AFB 61 (31-89) 98 (93-100)
Xpert MTB 92 (70-100) 99 (91-100)
Clinical Diagnosis* 24 (10-51) 94 (79-97)
* Clinical evaluation plus chest radiography after negative sputum smear microscopy or Xpert
REF: WHO Systematic Screening for Active Tuberculosis: Principles and Recommendations. WF 220, 2013
Sensitivity and Specificity of Testing
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